Medicine and Health Sciences Commons^™

Ectopic High Endothelial Venules In Pancreatic Ductal Adenocarcinoma: A Unique Site For Targeted Delivery., Baharak Bahmani, Mayuko Uehara, Farideh Ordikhani, Xiaofei Li, Liwei Jiang, Naima Banouni, Takaharu Ichimura, Vivek Kasinath, Siawosh K Eskandari, Nasim Annabi, Jonathan S Bromberg, Leonard D. Shultz, Dale L Greiner, Reza Abdi

Faculty Research 2018

BACKGROUND: Nanomedicine offers an excellent opportunity to tackle treatment-refractory malignancies by enhancing the delivery of therapeutics to the tumor site. High endothelial venules (HEVs) are found primarily in lymph nodes or formed de novo in peripheral tissues during inflammatory responses. They express peripheral node addressin (PNAd), which is recognized by the monoclonal antibody MECA79.

METHODS: Here, we demonstrated that HEVs form de novo in human pancreatic ductal adenocarcinoma (PDAC). We engineered MECA79 coated nanoparticles (MECA79-NPs) that recognize these ectopic HEVs in PDAC.

FINDINGS: The trafficking of MECA79-NPs following intravenous delivery to human PDAC implanted in a humanized mouse model was …

Assessing The Validity And Reliability Of A Freehand Tool Method For Analysis Of Ultrasound Cross-Sectional Area Images, Donald J. Marsh, Dylan Suarez, Luis Rodriguez-Castellano, Kyle Rochau, Ai Ishida, Caleb D. Bazyler

ETSU Faculty Works

No abstract provided.

Lakeshore Modification Reduces Secondary Production Of Macroinvertebrates In Littoral But Not Deeper Zones, Marlene Pätzig, Yvonne Vadeboncoeur, Mario Brauns

Biological Sciences Faculty Publications

Littoral macroinvertebrates are an integral component of lake food webs, but their productivity may be affected by shoreline alteration. We hypothesized that human modification of lake shores simplifies habitat diversity, which, in turn, affects littoral macroinvertebrate production and patterns of depth–production relationships. Furthermore, we expected that lakeshore modification would favor nonnative species, potentially compensating for negative effects of lakeshore modification on production of native taxa. To test these ideas, we estimated benthic macroinvertebrate production in the upper littoral, middle littoral, and profundal zones of a large lowland lake (Lake Scharmützelsee) in Northeast Germany. We collected samples between April and November …

Validity Of A Wireless Inertia Measurement Device In Quantifying Performance In Vertical Jumping Tests, Nicholas G. Anagnost, Alexandra Lates, John P. Wagle, Christopher B. Taber

Exercise Science Faculty Publications

The use of technology in sport and fitness training has rapidly become a tool for both athletes and coaches in monitoring performance variables for optimizing training stimulus and recovery (Duking, Hotho, Holmberg, Fuss, & Sperlich, 2016; Peake, Kerr & Sullivan, 2018). Wireless fitness trackers, GPS and accelerometry devices are growing in popularity with the athletic population outside of the clinical setting due to their lower cost and ease of use compared to traditional clinical measurement tools (Dellaserra, Gao & Ransdell, 2014). With the increased popularity of these devices comes the necessity to understand and validate the information collected from them …

Il-12 Gene Electrotransfer Triggers A Change In Immune Response Within Mouse Tumors, Guilan Shi, Chelsea Edelblute, Sezgi Arpag, Cathryn Lundberg, Richard Heller

Bioelectrics Publications

Metastatic melanoma is an aggressive skin cancer with a relatively low survival rate. Immune-based therapies have shown promise in the treatment of melanoma, but overall complete response rates are still low. Previous studies have demonstrated the potential of plasmid IL-12 (pIL-12) delivered by gene electrotransfer (GET) to be an effective immunotherapy for melanoma. However, events occurring in the tumor microenvironment following delivery have not been delineated. Therefore, utilizing a B16F10 mouse melanoma model, we evaluated changes in the tumor microenvironment following delivery of pIL-12 using different GET parameters or injection of plasmid alone. The results revealed a unique immune cell …

The Impact Of Whoop Technology On Sleep, Recovery, And Performance In Naia Baseball Players, Nolan Harms

Department of Teaching, Learning, and Teacher Education: Dissertations, Theses, and Student Research

Many key factors – including but not limited to – sleep, nutrition, travel, stress, and practice influence the optimization of athletic performance. Although previous studies have investigated the use of wearable technology in sport to track several such factors, peer-reviewed research specific to WHOOP technology is limited at best. The purpose of this study was to examine the impact of WHOOP technology on sleep, recovery, and batting performance in healthy NAIA baseball players. Data was collected over the course of 4 weeks of in-season play on 10 varsity NAIA baseball players (20.40 ± 0.97 years). All games – 18 total …

Effects Of Weightlifting Training On Isometric Mid-Thigh Pull Rate Of Force Development, Dylan G. Suarez, Kristina Ushakova, Satoshi Mizuguchi, Guy Hornsby, Michael H. Stone

ETSU Faculty Works

PURPOSE: To examine the influence of three distinct training phases on isometric mid-thigh pull (IMTP) measures in well-trained weightlifters. METHODS: Pre- and post-block IMTP data from 11 collegiate weightlifters was used for analysis. The mean of the best two attempts from each athlete for measures of PF and RFD from 0-50ms, 0-100ms, 0-150ms, 0-200ms, and 0-250ms were used for comparison. In total, results from five timepoints for each of the 11 athletes were examined in order to compare the effects of the three training phases. RESULTS: A repeated measures ANOVA revealed no statistically significant (p ≥ 0.05) effects of training …

Immediate Neurophysiological Effects Of Transcranial Electrical Stimulation, Anli Liu, Mihály Vöröslakos, Gregory Kronberg, Simon Henin, Matthew R. Krause, Yu Huang, Alexander Opitz, Ashesh Mehta, Christopher C. Pack, Bart Krekelberg, Antal Berényi, Lucas C. Parra, Lucia Melloni, Orrin Devinsky, György Buzsáki

Publications and Research

Noninvasive brain stimulation techniques are used in experimental and clinical fields for their potential effects on brain network dynamics and behavior. Transcranial electrical stimulation (TES), including transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS), has gained popularity because of its convenience and potential as a chronic therapy. However, a mechanistic understanding of TES has lagged behind its widespread adoption. Here, we review data and modelling on the immediate neurophysiological effects of TES in vitro as well as in vivo in both humans and other animals. While it remains unclear how typical TES protocols affect neural activity, we …

The Effect Of Altering Body Posture And Barbell Position On The Between-Session Reliability Of Force-Time Curve Characteristics In The Isometric Mid-Thigh Pull, Stuart N. Guppy, Claire J. Brady, Yosuke Kotani, Michael H. Stone, Nikola Medic, Guy Gregory Haff

ETSU Faculty Works

Seventeen strength and power athletes (n = 11 males, 6 females; height: 177.5 ± 7.0 cm, 165.8 ± 11.4 cm; body mass: 90.0 ± 14.1 kg, 66.4 ± 13.9 kg; age: 30.6 ± 10.4 years, 30.8 ± 8.7 years), who regularly performed weightlifting movements during their resistance training programs, were recruited to examine the effect of altering body posture and barbell position on the between-session reliability of force-time characteristics generated in the isometric mid-thigh pull (IMTP). After participants were familiarised with the testing protocol, they undertook two testing sessions which were separated by seven days. In each session, the participants …

Hdl In Endocrine Carcinomas: Biomarker, Drug Carrier, And Potential Therapeutic, Emily E. Morin, Xiang-An Li, Anna Schwendeman

Physiology Faculty Publications

High-density lipoprotein (HDL) have long been studied for their protective role against cardiovascular diseases, however recently relationship between HDL and cancer came into focus. Several epidemiological studies have shown an inverse correlation between HDL-cholesterol (HDL-C) and cancer risk, and some have even implied that HDL-C can be used as a predictive measure for survival prognosis in for specific sub-population of certain types of cancer. HDL itself is an endogenous nanoparticle capable of removing excess cholesterol from the periphery and returning it to the liver for excretion. One of the main receptors for HDL, scavenger receptor type B-I (SR-BI), is highly …

Development And Validation Of A Simple Convenience Store Shelf Audit., Tanya M. Horacek, Elif Dede Yildirim, Erin Kelly, Adrienne A. White, Karla P. Shelnutt, Kristin Riggsbee, Melissa D. Olfert, Jesse Morrell, Anne E. Matthews, Terezie T Mosby, Tandalayo Kidd, Kendra Kattelmann, Geoffrey Greene, Lisa Franzen-Castle, Sarah E. Colby, Carol Byrd-Bredbenner, Onikia Brown

Health and Nutritional Sciences Faculty Publications

ackground This paper describes the development, reliability, and convergent validity of a practical tool-the Convenience StoreSupportive Healthy Environment for Life-Promoting Food (SHELF) Audit. Methods Audit items included: a variety of fresh, processed, and frozen fruits and vegetables; low-fat dairy products; healthy staples and frozen meals; healthy food incentive programs; items sold in check-out areas; portion/cup sizes; and pricing. Each audit item was scored using a five-point semantic-differential scale (1 = provides little or no support for healthful foods to 5 = provides high support for healthful foods). Convergent validity was examined by comparing the SHELF audit to Ghirardelli et al. …

A Two Compartment Pharmacokinetic Model Describes The Intra‐Articular Delivery And Retention Of Rhprg4 Following Acl Transection In The Yucatan Mini Pig, Mark Hurtig, Iman Zaghoul, Heather Sheardown, Tannin A. Schmidt, Lina Liu, Ling Zhang, Khaled A. Elsaid, Gregory D. Jay

Pharmacy Faculty Articles and Research

Treatment of the injured joint with rhPRG4 is based on recent observations that inflammation diminishes expression of native PRG4. Re‐establishing lubrication between pressurized and sliding cartilage surfaces during locomotion promotes the nascent expression of PRG4 and thus intra‐articular (IA) treatment strategies should be supported by pharmacokinetic evidence establishing the residence time of rhPRG4. A total of 21 Yucatan minipigs weighing ∼55 Kg each received 4 mg of 131I‐rhPRG4 delivered by IA injection 5 days following surgical ACL transection. Animals were sequentially euthanized following IA rhPRG4 at 10 mins (time zero), 24, 72 hrs, 6, 13 and 20 days later. The …

Macrophage-Derived Netrin-1 Promotes Abdominal Aortic Aneurysm Formation By Activating Mmp3 In Vascular Smooth Muscle Cells, Tarik Hadi, Ludovic Boytard, Michele Silvestro, Dornazsadat Alebrahim, Samson Jacob, Jordyn Feinstein, Krista Barone, Wes Spiro, Susan Hutchison, Russell Simon, Debra L. Rateri, Florence Pinet, David Fenyo, Mark Adelman, Kathryn J. Moore, Holger K. Eltzschig, Alan Daugherty, Bhama Ramkhelawon

Physiology Faculty Publications

Abdominal aortic aneurysms (AAA) are characterized by extensive extracellular matrix (ECM) fragmentation and inflammation. However, the mechanisms by which these events are coupled thereby fueling focal vascular damage are undefined. Here we report through single-cell RNA-sequencing of diseased aorta that the neuronal guidance cue netrin-1 can act at the interface of macrophage-driven injury and ECM degradation. Netrin-1 expression peaks in human and murine aneurysmal macrophages. Targeted deletion of netrin-1 in macrophages protects mice from developing AAA. Through its receptor neogenin-1, netrin-1 induces a robust intracellular calcium flux necessary for the transcriptional regulation and persistent catalytic activation of matrix metalloproteinase-3 (MMP3) …

The Roles Of Primary Cilia In Cardiovascular Diseases, Rajasekharreddy Pala, Maha Jamal, Qamar Alshammari, Surya M. Nauli

Pharmacy Faculty Articles and Research

Primary cilia are microtubule-based organelles found in most mammalian cell types. Cilia act as sensory organelles that transmit extracellular clues into intracellular signals for molecular and cellular responses. Biochemical and molecular defects in primary cilia are associated with a wide range of diseases, termed ciliopathies, with phenotypes ranging from polycystic kidney disease, liver disorders, mental retardation, and obesity to cardiovascular diseases. Primary cilia in vascular endothelia protrude into the lumen of blood vessels and function as molecular switches for calcium (Ca2+) and nitric oxide (NO) signaling. As mechanosensory organelles, endothelial cilia are involved in blood flow sensing. Dysfunction in endothelial …

A Rapid And Sensitive System For Recovery Of Nucleic Acids From Mycobacteria Sp. On Archived Glass Slides, Balkis A. Talip, William J. Snelling, Roy D. Sleator, Colm Lowery, James S.G. Dooley

Department of Biological Sciences Publications

The field of diagnostics continues to advance rapidly with a variety of novel approaches, mainly dependent upon high technology platforms. Nonetheless much diagnosis, particularly in developing countries, still relies upon traditional methods such as microscopy. Biological material, particularly nucleic acids, on archived glass slides is a potential source of useful information both for diagnostic and epidemiological purposes. There are significant challenges faced when examining archived samples in order that an adequate amount of amplifiable DNA can be obtained. Herein, we describe a model system to detect low numbers of bacterial cells isolated from glass slides using (laser capture microscopy) LCM …

Comparison Between Kinetic And Kinetic-Kinematic Driven Knee Joint Finite Element Models, Paul O. Bolcos, Mika E. Mononen, Ali Mohammadi, Mohammadhossein Ebrahimi, Matthew S. Tanaka, Michael A. Samaan, Richard B. Souza, Xiaojuan Li, Juha-Sampo Suomalainen, Jukka S. Jurvelin, Juha Töyräs, Rami K. Korhonen

Kinesiology and Health Promotion Faculty Publications

Use of knee joint finite element models for diagnostic purposes is challenging due to their complexity. Therefore, simpler models are needed for studies where a high number of patients need to be analyzed, without compromising the results of the model. In this study, more complex, kinetic (forces and moments) and simpler, kinetic-kinematic (forces and angles) driven finite element models were compared during the stance phase of gait. Patella and tendons were included in the most complex model, while they were absent in the simplest model. The greatest difference between the most complex and simplest models was observed in the internal-external …

Food Safety Knowledge And Practices Among Saudi Mothers, Wafa O. Ayaz, Anushree Priyadarshini, Amit Jaiswal

Articles

This study examines food safety knowledge and practices of mothers in Saudi Arabia. A total of 979 respondents participated in the study and completed a questionnaire that accessed their knowledge of food storage, food handling, usage and maintenance of kitchen facilities, personal hygiene and food poisoning. Results showed that mothers in Saudi Arabia had moderate knowledge of food storage (passing rate 64.9%) and usage and maintenance of kitchen facilities (passing rate 66.5%). While they had good knowledge of personal hygiene (passing rate 83.8%) and food poisoning (passing rate 78.5%), their knowledge with regard to food handling was poor (passing rate …

Mitochondrial Metabolism In Major Neurological Diseases, Zhengqiu Zhou, Grant L. Austin, Lyndsay E. A. Young, Lance A. Johnson, Ramon Sun

Molecular and Cellular Biochemistry Faculty Publications

Mitochondria are bilayer sub-cellular organelles that are an integral part of normal cellular physiology. They are responsible for producing the majority of a cell’s ATP, thus supplying energy for a variety of key cellular processes, especially in the brain. Although energy production is a key aspect of mitochondrial metabolism, its role extends far beyond energy production to cell signaling and epigenetic regulation–functions that contribute to cellular proliferation, differentiation, apoptosis, migration, and autophagy. Recent research on neurological disorders suggest a major metabolic component in disease pathophysiology, and mitochondria have been shown to be in the center of metabolic dysregulation and possibly …

Detection Of Correlated Hidden Factors From Single Cell Transcriptomes Using Iteratively Adjusted-Sva (Ia-Sva)., Donghyung Lee, Anthony Cheng, Nathan Lawlor, Mohan Bolisetty, Duygu Ucar

Faculty Research 2018

Single cell RNA-sequencing (scRNA-seq) precisely characterizes gene expression levels and dissects variation in expression associated with the state (technical or biological) and the type of the cell, which is averaged out in bulk measurements. Multiple and correlated sources contribute to gene expression variation in single cells, which makes their estimation difficult with the existing methods developed for batch correction (e.g., surrogate variable analysis (SVA)) that estimate orthogonal transformations of these sources. We developed iteratively adjusted surrogate variable analysis (IA-SVA) that can estimate hidden factors even when they are correlated with other sources of variation by identifying a set of genes …

Quantitative Gadolinium-Free Cardiac Fibrosis Imaging In End Stage Renal Disease Patients Reveals A Longitudinal Correlation With Structural And Functional Decline, Tori A. Stromp, Tyler J. Spear, Rebecca M. Holtkamp, Kristin N. Andres, Joshua C. Kaine, Wissam H. Alghuraibawi, Steve W. Leung, Brandon K. Fornwalt, Moriel H. Vandsburger

Physiology Faculty Publications

Patients with end stage renal disease (ESRD) suffer high mortality from arrhythmias linked to fibrosis, but are contraindicated to late gadolinium enhancement magnetic resonance imaging (MRI). We present a quantitative method for gadolinium-free cardiac fibrosis imaging using magnetization transfer (MT) weighted MRI, and probe correlations with widely used surrogate markers including cardiac structure and contractile function in patients with ESRD. In a sub-group of patients who returned for follow-up imaging after one year, we examine the correlation between changes in fibrosis and ventricular structure/function. Quantification of changes in MT revealed significantly greater fibrotic burden in patients with ESRD compared to …

H3k9 Methyltransferases And Demethylases Control Lung Tumor-Propagating Cells And Lung Cancer Progression, S. P. Rowbotham, F Li, A. F. M. Dost, S. M. Louie, B. P. Marsh, P. Pessina, C. R. Anbarasu, Christine Fillmore Brainson, S. J. Tuminello, A. Lieberman, S. Ryeom, T. M. Schlaeger, B. J. Aronow, H. Watanabe, K. K. Wong, C. F. Kim

Toxicology and Cancer Biology Faculty Publications

Epigenetic regulators are attractive anticancer targets, but the promise of therapeutic strategies inhibiting some of these factors has not been proven in vivo or taken into account tumor cell heterogeneity. Here we show that the histone methyltransferase G9a, reported to be a therapeutic target in many cancers, is a suppressor of aggressive lung tumor-propagating cells (TPCs). Inhibition of G9a drives lung adenocarcinoma cells towards the TPC phenotype by de-repressing genes which regulate the extracellular matrix. Depletion of G9a during tumorigenesis enriches tumors in TPCs and accelerates disease progression metastasis. Depleting histone demethylases represses G9a-regulated genes and TPC phenotypes. Demethylase inhibition …

Military-Related Exposures, Social Determinants Of Health, And Dysbiosis: The United States-Veteran Microbiome Project (Us-Vmp), Lisa A. Brenner, Andrew J. Hoisington, Kelly A. Stearns-Yoder, Christopher E. Stamper, Jared A. Heinze, Teodor T. Postolache, Daniel A. Hadidi, Claire A. Hoffmire, Maggie A. Stanislawski

Faculty Publications

Significant effort has been put forth to increase understanding regarding the role of the human microbiome in health- and disease-related processes. In turn, the United States (US) Veteran Microbiome Project (US-VMP) was conceptualized as a means by which to serially collect microbiome and health-related data from those seeking care within the Veterans Health Administration (VHA). In this manuscript, exposures related to military experiences, as well as conditions and health-related factors among patients seen in VHA clinical settings are discussed in relation to common psychological and physical outcomes. Upon enrollment in the study, Veterans complete psychometrically sound (i.e., reliable and valid) …

The Effect Of Coronal Prosthetic Alignment Changes On Socket Reaction Moments, Spatiotemporal Parameters, And Perception Of Alignment During Gait In Individuals With Transtibial Amputation, Hiroshi Hashimoto, Toshiki Kobayashi, Fan Gao, Masataka Kataoka, Kuniharu Okuda

Kinesiology and Health Promotion Faculty Publications

Introduction: The alignment of a prosthesis is clinically determined based on observations by clinicians and the subjective perception of amputees during gait. However, this process has been reported to be unreliable. Socket reaction moment has been reported to be significantly impacted by alignment changes, but the impact of these alignment changes on other gait parameters is unclear. The aim of this study was to investigate the effects of coronal alignment changes of a transtibial prosthesis on socket reaction moment, spatiotemporal parameters, and perceptions of alignment during gait in amputees.

Methods: Nine individuals with transtibial amputation participated in this study. Socket …

Improved Reference Genome For The Domestic Horse Increases Assembly Contiguity And Composition, Theodore S. Kalbfleisch, Edward S. Rice, Michael S. Depriest Jr., Brian P. Walenz, Matthew S. Hestand, Joris R. Vermeesch, Brendan L. O'Connell, Ian T. Fiddes, Alisa O. Vershinina, Nedda F. Saremi, Jessica L. Petersen, Carrie J. Finno, Rebecca R. Bellone, Molly E Mccue, Samantha A. Brooks, Ernest Bailey, Ludovic Orlando, Richard E. Green, Donald C. Miller, Douglas F. Antczak, James N. Macleod

Maxwell H. Gluck Equine Research Center Faculty Publications

Recent advances in genomic sequencing technology and computational assembly methods have allowed scientists to improve reference genome assemblies in terms of contiguity and composition. EquCab2, a reference genome for the domestic horse, was released in 2007. Although of equal or better quality compared to other first-generation Sanger assemblies, it had many of the shortcomings common to them. In 2014, the equine genomics research community began a project to improve the reference sequence for the horse, building upon the solid foundation of EquCab2 and incorporating new short-read data, long-read data, and proximity ligation data. Here, we present EquCab3. The count of …

Waardenburg Syndrome And Left Persistent Superior Vena Cava, Driss Raissi, Alexander Christie, Kimberly Applegate

Radiology Faculty Publications

Waardenburg syndrome (WS) is a rare genetic disorder secondary to neural crest cell developmental abnormalities. It is predominantly described as an auditory-pigmentary syndrome with diverse patient presentation, typically involving congenital sensorineural hearing loss and pigmentation abnormalities of the skin, hair, and iris. Other developmental abnormalities that may be associated with this syndrome are Hirschsprung's disease and a myriad of cardiovascular congenital defects. We present a case of a young girl with WS who found to have a persistent left superior vena cava (PLSVC) draining into the coronary sinus. The prevalence of PLSVC is increased in patients with chromosomal and genetic …

Does A Vegan Diet Contribute To Prevention Or Maintenance Of Diseases?, Malia K. Burkholder, Danae A. Fields

Exercise Science Senior Research Projects

This literature review deals with the topic of, does a vegan diet contribute to prevention or maintenance of diseases? Our main focus was to look at what a vegan diet entailed, the history of veganism, and why people decide to adhere to this diet type. Multiple research studies were looked over on the topics of how a vegan diet effects the disease processes of cancer, diabetes, gastral intestinal issues, weight loss, and heart disease. The overall arching theme that was found in the research is that a vegan diet is beneficial in helping to lessen the risk or aid in …

Hnrnpa2 Mediated Acetylation Reduces Telomere Length In Response To Mitochondrial Dysfunction, Manti Guha, Satish Srinivasan, F. Bradley Johnson, Gordon Ruthel, Kip Guja, Miguel Garcia-Diaz, Brett A. Kaufman, M. Rebecca Glineburg, Jikang Fang, Hiroshi Nakagawa, Jeelan Basha, Tapas Kundu, Narayan G. Avadhani

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Telomeres protect against chromosomal damage. Accelerated telomere loss has been associated with premature aging syndromes such as Werner’s syndrome and Dyskeratosis Congenita, while, progressive telomere loss activates a DNA damage response leading to chromosomal instability, typically observed in cancer cells and senescent cells. Therefore, identifying mechanisms of telomere length maintenance is critical for understanding human pathologies. In this paper we demonstrate that mitochondrial dysfunction plays a causal role in telomere shortening. Furthermore, hnRNPA2, a mitochondrial stress responsive lysine acetyltransferase (KAT) acetylates telomere histone H4at lysine 8 of (H4K8) and this acetylation is associated with telomere attrition. Cells containing dysfunctional mitochondria …

Myeloablative Vs Reduced-Intensity Conditioning Allogeneic Hematopoietic Cell Transplantation For Chronic Myeloid Leukemia, Saurabh Chhabra, Kwang Woo Ahn, Zhen-Huan Hu, Sandeep Jain, Amer Assal, Jan Cerny, Edward A. Copelan, Andrew Daly, Zachariah Defilipp, Shahinaz M Gadalla, Robert Peter Gale, Siddhartha Ganguly, Betty K. Hamilton, Gerhard C. Hildebrandt, Jack W. Hsu, Yoshihiro Inamoto, Abraham S. Kanate, H. Jean Khoury, Hillard M. Lazarus, Mark R. Litzow, Sunita Nathan, Richard F. Olsson, Attaphol Pawarode, Olle Ringden, Jacob M. Rowe, Ayman Saad, Bipin N. Savani, Harry C. Schouten, Sachiko Seo, Nirav N. Shah

Markey Cancer Center Faculty Publications

Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment of chronic myeloid leukemia (CML). Optimal conditioning intensity for allo-HCT for CML in the era of tyrosine kinase inhibitors (TKIs) is unknown. Using the Center for International Blood and Marrow Transplant Research database, we sought to determine whether reduced-intensity/nonmyeloablative conditioning (RIC) allo-HCT and myeloablative conditioning (MAC) result in similar outcomes in CML patients. We evaluated 1395 CML allo-HCT recipients between the ages of 18 and 60 years. The disease status at transplant was divided into the following categories: chronic phase 1, chronic phase 2 or greater, and accelerated phase. Patients …

Modulation Of Auxin And Cytokinin Responses By Early Steps Of The Phenylpropanoid Pathway, Jasmina Kurepa, Timothy E. Shull, Sumudu S. Karunadasa, Jan A. Smalle

Plant and Soil Sciences Faculty Publications

Background: The phenylpropanoid pathway is responsible for the synthesis of numerous compounds important for plant growth and responses to the environment. In the first committed step of phenylpropanoid biosynthesis, the enzyme phenylalanine ammonia-lyase (PAL) deaminates L-phenylalanine into trans-cinnamic acid that is then converted into p-coumaric acid by cinnamate-4-hydroxylase (C4H). Recent studies showed that the Kelch repeat F-box (KFB) protein family of ubiquitin ligases control phenylpropanoid biosynthesis by promoting the proteolysis of PAL. However, this ubiquitin ligase family, alternatively named Kiss Me Deadly (KMD), was also implicated in cytokinin signaling as it was shown to promote the degradation of …

Lestaurtinib Is A Potent Inhibitor Of Anaplastic Thyroid Cancer Cell Line Models, Nicole Pinto, Stephenie D. Prokopec, Frederick Vizeacoumar, Karlee Searle, Matthew Lowerison, Kara M. Ruicci, John Yoo, Kevin Fung, Danielle Macneil, Jim C. Lacefield, Hon S. Leong, Joe S. Mymryk, John W. Barrett, Alessandro Datti, Paul C. Boutros, Anthony C. Nichols

Anatomy and Cell Biology Publications

Anaplastic thyroid cancer (ATC) is a rare and lethal human malignancy with no known effective therapies in the majority of cases. Despite the use of conventional treatments such as chemotherapy, radiation and surgical resection, this disease remains almost universally fatal. In the present study, we identified the JAK2 inhibitor Lestaurtinib as a potent compound when testing against 13 ATC cell lines. Lestaurtinib demonstrated a potent antiproliferative effect in vitro at nanomolar concentrations. Furthermore, Lestaurtinib impeded cell migration and the ability to form colonies from single cells using scratch-wound and colony formation assays, respectively. Flow cytometry was used for cell cycle …